Interpretive Summary: This study evaluated influenza vaccines in pigs. Vaccines included inactivated (killed) and live virus exposure with two different isolates of swine influenza virus (SIV) of the H1 subtype. The killed vaccines provided complete protection against challenge with live virus that was the same as that contained in the vaccine. However, one of the killed vaccines did not protect against live virus challenge with the different SIV isolate. All of the pigs in this group were shown microscopically to have virus distributed throughout the lung in contrast to control pigs. In addition, pneumonia caused by the influenza virus was dramatically worse in one-third of the pigs receiving the mismatched vaccine. In contrast, live virus exposure followed by challenge with the different influenza virus was completely protective. This study suggests that immunity to influenza virus is complex and there may be a risk of enhancing disease when the inactivated vaccine virus is mismatched with the challenge virus.

Technical Abstract:
We evaluated two US swine influenza virus (SIV) isolates, A/Swine/Iowa/15/1930 H1N1 (IA30) and A/Swine/Minnesota/00194/2003 H1N2 (MN03), with substantial genetic variation in the HA gene and failure to cross-react in the hemagglutination inhibition (HI) assay, in an in vivo vaccination and challenge model. Inactivated vaccines were prepared from each isolate and used to immunize conventional pigs, followed by challenge with homologous or heterologous virus. Both inactivated vaccines provided complete protection against homologous challenge and the MN03 vaccine provided partial protection against IA30. However, the IA30 vaccine failed to protect against the heterologous MN03 challenge. Three of the nine pigs in this group had substantially greater percentages of lung lesions, suggesting the IA30 inactivated vaccine potentiated the pneumonia caused by the MN03 challenge. In contrast, priming with live IA30 virus provided protection from nasal shedding and virus replication in the lung in MN03 challenged pigs. These data indicate that divergent H1 viruses that do not cross-react serologically may not provide complete cross-protection when used in inactivated vaccines against heterologous challenge. In addition, live virus infection can confer protection against heterologous challenge.